Insulin resistance (IR) is a condition in which the body's cells become less sensitive to the glucose-lowering effects of the hormone insulin. The common underlying causes of insulin resistance are largely unidentified, however both inherited and acquired influences are likely to be involved. Environmental factors such as physical inactivity, abdominal obesity, diet (e.g., high calorie intake), medications (e.g., Cortisol), hyperglycaemia (glucose toxicity), increased free fatty acids, and the aging process may also contribute. The most common type of insulin resistance is associated with obesity resulting in a condition known as metabolic syndrome.
In an insulin-resistant person, normal levels of insulin do not have the same effect in controlling blood glucose levels. During the compensated phase in insulin resistance insulin levels are higher, and blood glucose levels are largely maintained. Therefore, in most people with insulin resistance there are normal levels of glucose in the blood but high levels of insulin in the blood. If compensatory insulin secretion fails, then either fasting (impaired fasting glucose) or postprandial (impaired glucose tolerance) blood glucose concentrations increase. Eventually, Type 2 diabetes occurs when blood glucose levels become higher throughout the day as the resistance increases and compensatory insulin secretion fails.
In pre-diabetes, insulin becomes less effective at stimulating metabolism of glucose. Pre-diabetics may be detectable as early as 20 years before diabetic symptoms become evident. Studies have shown that although patients typically show very few symptoms, long-term physiological damage is already occurring at this stage. Up to 60% of these individuals will progress to Type 2 diabetes within 10 years.
Diabetes mellitus is a metabolic disease that is brought about by either the insufficient production of insulin or the inability of the body to properly respond to insulin. Insulin is produced by the pancreas and is the principal hormone that regulates the uptake of glucose from the blood into cells and inhibits the production of glucose from the liver. Therefore deficiency of insulin production or the insensitivity to its actions plays a key role in all forms of diabetes. Insulin deficiencies, the insensitivity of insulin receptors, or a combination of both play a central role in both Type 1 and Type 2 forms of diabetes mellitus. Type 1 diabetes mellitus is caused by a decrease in the number of insulin-producing cells in the islets of Langerhans in the pancreas. Type 2 diabetes mellitus is generally characterized by the body's resistance to insulin, caused by the loss or diminished function of insulin receptors that mediate the entrance of insulin into the body's cells. Type 2 diabetes occurs commonly in association with other disorders such as hypertension, dyslipidaemia (includes high LD1 cholesterol, low HDL cholesterol, and high triglycerides) and hypercoagulability. All these problems usually occur in association with obesity, especially abdominal obesity.
There exists a need for new and/or improved treatments for conditions associated with impaired response to insulin and/or glucose metabolism.
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